A homozygote variant in the tRNA splicing endonuclease subunit 54 causes pontocerebellar hypoplasia in a consanguineous Iranian family

Molecular Genetics & Genomic Medicine

卷:8

Ehsan Razmara¹  Mohammad Galehdari²  Fatemeh Bitarafan³  Navid Almadani⁴  Masoud Garshasbi⁵  Afrooz Sepahvand⁶  Ali Reza Tavasoli⁷ 

[1] Australian Regenerative Medicine Institute Monash University Clayton VIC Australia;

[2] Department of Biology Faculty of Sciences North Tehran Branch Islamic Azad University Tehran Iran;

[3] Department of Cellular and Molecular Biology North Tehran Branch Islamic Azad University Tehran Iran;

[4] Department of Genetics Reproductive Biomedicine Research Center Royan Institute for Reproductive BiomedicineACECR Tehran Iran;

[5] Department of Medical Genetics Faculty of Medical Sciences Tarbiat Modares University Tehran Iran;

[6] Faculty of Advanced Science and Technology Tehran Medical Sciences Islamic Azad University Tehran Iran;

[7] Myelin Disorders Clinic Pediatric Neurology Division Children's Medical Center Pediatrics Center of Excellence Tehran University of Medical Sciences Tehran Iran;

关键词: PCR‐RFLP;    pontocerebellar hypoplasias;    synonymous variant;    TSEN54;    whole‐exome sequencing;   

DOI  :  10.1002/mgg3.1413

来源: DOAJ

【 摘 要 】

Abstract Background Homozygous loss‐of‐function mutations in TSEN54 (tRNA splicing endonuclease subunit 54; OMIM: 608755) cause different types of pontocerebellar hypoplasias (PCH) including PCH2, PCH4, and PCH5. The study aimed to determine the possible genetic factors contributing to PCH phenotypes in two affected male infants in an Iranian family. Methods We subjected two affected individuals in a consanguineous Iranian family. To systematically investigate the susceptible gene(s), whole‐exome sequencing was performed on the proband and a novel identified variant was confirmed by Sanger sequencing. We also analyzed 26 relatives in three generations using PCR‐restriction fragment length polymorphism (PCR‐RFLP) followed and confirmed by Sanger sequencing. Results Physical and medical examinations confirmed PCH in the patients. Besides, the proband showed bilateral moderate sensorineural hearing loss and structural heart defects as the novel phenotypes. The molecular findings also verified that two affected individuals were homozygote for the novel synonymous variant, NM_207346.2: c.1170G>A; p.(Val390Val), in TSEN54. PCR‐RFLP and Sanger sequencing elucidated that the parents and 16 relatives were heterozygote for the novel variant. Conclusion We identified a novel synonymous variant, c.1170G>A, in TSEN54 associated with PCH in an Iranian family. Based on this study, we strongly suggest using “TSENopathies” to show the overlapped phenotypes among different types of PCH resulted from TSEN causative mutations.

【 授权许可】

Unknown